The vertebrate retina is a highly organized neural structure where the basic identity and function of individual cell types have been established. Although much is known about the basic structure and function of the retina, much less is known about the events that influence how its neurons differentiate and find their synaptic partners. The zebrafish is an excellent model system to study these events. Embryos develop rapidly and their transparency enables direct visualization of retinal neurons from their birth to maturity. Furthermore, the genetics of this model organism, and the ability to easily manipulate the embryo, allow probing of the molecular mechanisms behind observed cellular behaviors. This study will employ a newly created a method to conditionally ablate specific cells in transgenic zebrafish. This technology permits modeling of cell loss at any stage of development and can be used to mimic degenerative disease states. These transgenic fish will show how loss of a single cell type affects the developing retina. This system will also inform us about differentiation and circuit assembly during regeneration. Unlike mammals, zebrafish can extensively regenerate damaged tissue. Using this technology will allow us to monitor differentiation and synapse formation during regeneration of the vertebrate nervous system. Understanding how this process occurs in fish may eventually help us modulate regenerative capacity in human neural degenerative diseases. PUBLIC HEALTH RELEVANCE: This project will explore how neurons in the retina behave during normal development, degeneration, and regeneration in zebrafish. Understanding how this process occurs in fish may eventually help us modulate regenerative capacity in human neural degenerative diseases.